Abstract Fetal Alcohol Spectrum Disorders (FASD) affects up to 5% of births in the US each year and results in life-long physical and behavioral impairments. Neurulation-stage ethanol exposure (~ 4th week of pregnancy in humans, gestational days 8-10 in mice), is associated with a widening of the face and brain, particularly the ventral midline structures (e.g. septum, pituitary, ventricles), and neurofunctional changes later in life. This expansion is similar to the CNS and craniofacial abnormalities observed in ciliopathic genetic disorders such as Joubert?s syndrome. Ciliopathies are a consequence of defects in primary cilia, immotile sensory organelles critical for sonic hedgehog (Shh) pathway transduction and cell proliferation during development. Cilia dysfunction in some ciliopathies results in an overactivation of Shh, leading to the observed CNS anomalies. Previous work has suggested that mutations in cilia-associated motor proteins lead to ciliopathic phenotypes and interact with ethanol to cause wider brains (unpublished data). In this proposal, we use a well-characterized mouse model of FASD to test the hypothesis that ethanol exposure during neurulation induces a ?transient? ciliopathy in the embryo, leading to the shared phenotype between ciliopathies and FASD. Aim 1 analyzes primary cilia number and morphology in the neural tube following neurulation-stage ethanol exposure. Aim 2 investigates the mechanisms of these ciliary defects by examining cilia-related gene expression changes. Finally, Aim 3 examines whether neurulation-stage ethanol exposure alters cilia stability and function through analysis of tubulin post-translational modifications and Shh pathway signaling. Preliminary data suggest that ethanol- exposed embryos have altered expression of key ciliogenesis genes and an increased number of cilia in the neural tube. Presence of more cilia would lead to upregulated Shh signaling and abnormal cell proliferation, causing the observed CNS abnormalities. Importantly, these experiments will provide evidence supporting alterations to primary cilia number and function in the neural tube as a novel pathway through which ethanol exposure causes symptoms of FASD.